Human serum contains a unique set of proteins with affinity for DNA. Initial characterization of these DNA-binding proteins has indicated their universal occurrence and alterations of these proteins have been found in malignant diseases. The primary foci of this research are the complete biochemical, immunological, and genetic study of the major species of DNA-binding proteins resident in normal human serum and the identification and characterization of the DNA-binding proteins with potential as tumor markers or indicators of other disease states. Current stuides will emphasize the nature of the DNA-protein interactions specific to the serum DNA-binding proteins with emphasis on the localization of the actual DNA-binding domains; such studies are ultimately directed toward a correlation of the DNA-binding ability of these proteins with physiological functions. Secondly, there will be a continued evaluation of the diagnostic or prognostic potential of serum DNA-binding proteins with particular regard to the malignancy-associated c3DP protein. Thirdly, studies will be made to correlate DNA-binding protein of chromosomal origin with their serum counterparts.